LC-NE and DR-5-HT structure and function
nemo:prj-uy7joas · Short name: cohen_lcne_dr5ht_proj
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Norepinephrine (NE) and serotonin (5-HT) are released through most of the central nervous system by neurons in the locus coeruleus (LC) and dorsal raphe (DR), respectively. We are studying the structure and function of these neurons in mice using multiple measurements: single-neuron morphological reconstructions, sequencing-based analysis of projections (MAPseq), single-cell RNA sequencing, ex vivo membrane potential measurements with gene expression analysis (""Patch-seq""), and activity during behavior. We find a relationship between the structure and function of LC-NE neurons. Axonal projections of individual neurons were largely confined within brain regions and organized along a dorsal-ventral axis. Projections correlated with graded gene expression in LC. Electrophysiological and calcium sensor recordings during a behavioral task requiring ongoing learning showed that neurons in dorsal LC projecting to the cerebral cortex were excited by reward prediction error, a key signal driving learning, and predicted future changes in behavior. Neurons in ventral LC were excited by lack of reward and predicted the opposite changes in future behavior. Together, these observations reveal a graded structure and function of a neurotransmitter system and show that it contains a quantitative learning signal for flexible behavior.
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